TheEGF receptor family: spearheading a merger of signaling and therapeutics
TheEGF receptor family: spearheading a merger of signaling and therapeutics
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DOI：
10.1016/j.ceb.2007.02.008
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发表时间：
2007-04-01
影响因子：
7.5
通讯作者：
Yarden, Yosef
中科院分区：
文献类型：
--
作者：
Bublil, Erez M.;Yarden, Yosef
ErbB受体酪氨酸激酶进化为关键的调控实体，使细胞外环境与细胞内机制沟通，在不断变化的环境中产生适当的生物反应。自发现以来，ErbB家族的许多方面已经被破译；重点是人类疾病中的信号畸变。然而，只有现在，随着这些受体的原子坐标的可用性，我们才能构建一个完整的配体诱导受体二聚化和随后的酪氨酸激酶激活机制的模型。此外，最近引入的新的高通量筛选方法，结合系统生物学观点的实现，揭示了压倒性的网络复杂性，实现了强大的信号和进化性。这一知识可能会影响我们对疾病的看法，即系统扰动和对erbb靶向治疗的抵抗是稳健性的表现。
The ErbB receptor tyrosine kinases evolved as key regulatory entities enabling the extracellular milieu to communicate with the intracellular machinery to bring forth the appropriate biological response in an ever-changing environment. Since its discovery, many aspects of the ErbB family have been deciphered; with emphasis on aberration of signaling in human diseases. However, only now, with the availability of the atomic coordinates of these receptors, can we construct a comprehensive model of the mechanisms underlying ligand-induced receptor dimerization and subsequent tyrosine kinase activation. Furthermore, the recent introduction of new high-throughput screening methodologies, combined with the materialization of a systems biology perspective, reveals an overwhelming network complexity, enabling robust signaling and evolvability. This knowledge is likely to impact our view of diseases as system perturbations and resistance to ErbB-targeted therapeutics as manifestations of robustness.